Microplastics, Cirrhosis and Portal Hypertension

Official title

The Impact of Microplastics and Nanoplastics on Liver Health and Cardiovascular Diseases in India

Overview

Cirrhosis and portal hypertension are associated with an hyperdynamic circulation and hepatic inflammation, leading to complications like ascites, variceal bleeding, acute kidney injury, and higher infection risk. Microplastics (MPs) are a global plastic pollution issue, and studies have found plastic MPs or nanoparticles (NPs) contaminating human, animal and environmental ecosystems.It has been noted that the accumulation of MPs increases with a reduction in size of the plastic particle. MPs are categorized into primary particles such as manufactured plastics including pellets and cosmetic microbeads and secondary particles which originate from mechanical and ultraviolet disruption of large plastic particles. MPs can be ingested via food or beverages, especially plastic packaged comestibles or inhaled as environmental pollutants. Contamination of medications such as antibiotics, intravenous fluids, albumin and medical devices is another source of exposure to microplastics in patients with chronic liver disease (CLD)In particular exposure to endoscopic interventions, liver biopsy, and invasive procedures such as paracentesis and interventional radiology procedures can lead to plastic exposure and deposition of MPs in the liver and other tissues in patients with cirrhosis. It may be hypothesized that these may contribute to hepatic inflammation and progression of cirrhosis and portal hypertension. Globally, there is new research on the influence of MPs on the environment, plant and animal ecosystems and human health. Polystyrene (PS) microspheres that concentrate in the liver, intestine and the kidneys of mammals disrupt lipid and energy metabolism, impair mucus secretion, and alter the microbiome. Therefore, studies are required to assess how and to what extent, MPs impact human health, and affect chronic diseases like cirrhosis and reduce longevity. The study investigators will assess the presence of MPs in the liver, kidneys and intestine of patients with liver cirrhosis and compare it with those without underlying liver disease and determine the impact on portal hypertension and fibrosis, and cardiovascular and metabolic function.

Detailed description

First, because the methodology requires chemical digestion, it is unclear where in the liver MPs are deposited. For instance, it is indeterminate if MPs are deposited intracellularly, in Kupffer cells, endothelium or hepatocytes/cholangiocytes. In the present study histopathological assessments of the liver tissue will be performed to determine the presence of the MPs.

* Furthermore, the study will assess various polymer types of MP in cirrhotic liver tissue including commonly observed plastic polymers PS (polystyrene), PE (polyethylene), PP (polypropylene), PVC (polyvinyl chloride), PET (polyethylene terephthalate), PC (polycarbonate), and PMMA (polymethyl methacrylate). * Therefore, potential cellular sites of deposition in the liver will be assessed. If the MPs were in the systemic circulation, without any liver parenchymal residues, such particles should also be identified in spleen and kidney samples. * histopathology and electron microscopy of the liver tissue which should clarify the specific accumulation sites.

Interventions

• Diagnostic test Assessment of microplastics in tissue
  After meeting inclusion and exclusion criteria, 30 patients with cirrhosis will be included in this study with written informed consent from patient (surgical cases) or scheduled liver biopsy. Diagnosis of chronic liver disease will be based on history, physical examination, laboratory investigations, upper gastrointestinal endoscopy as recorded in the patient file, imaging studies (ultrasonography and doppler of splenoportal venous axis). Underlying etiology of liver disease will be recorded. C

Primary outcome measures

• The primary outcome is to assess MPs in human liver tissue, analysing their morphology, size, and composition (4-30 µm) in tissue samples from the liver inpatients with cirrhosis as compared with controls without cirrhosis [Time frame: At time of enrolment]

Secondary outcome measures (3)

• • Identification of Various polymer types, including PS, PVC, PET, PMMA, POM, and PP and surface alterations indicative of long-term deposition. [Time frame: At enrolment]
• • Determination of plastic pollution exposure in patients with cirrhosis by detailed history of diet, oral and parenteral medication, interventions including prior biopsy and endoscopy [Time frame: At the time of elective endoscopy]
• Assessment of micronanoplastics in peripheral blood [Time frame: At enrolment]

Eligibility criteria

Inclusion criteria

• Age range of 18-70 years
• Cirrhosis, as diagnosed by histology or clinical, laboratory and USG findings.
• Undergoing elective surgery or liver transplantation

Exclusion criteria

• • Hepatocellular carcinoma

• Pregnancy or lactation
• Patients with HIV or retroviral therapy
• Prior liver interventions like locoregional therapy, presence of HCC, prior abdominal surgery

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Observational model

Case-control

Study locations

India · 2 centers

• Dr. Madhumita Premkumar — Chandigarh
• PGIMER Chandigarh — Chandigarh

Identifiers

NCT: NCT07280390 · PGI/IEC/2025/EIC000779

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗